We have found that 83 percent of patients with metastatic breast or lung cancers who have received prior therapy are rheumatoid factor (RF) seropositive. In contrast, patients with similar but untreated tumors and irrespective of prior therapy, patients with brain tumors or multiple myeloma, are usually seronegative. This observation assumed immediate relevance to tumor-host interaction when we found that RF, immunologically isolated from the plasma of patients with rheumatoid arthritis, is toxic to cells from many tumors. First, we wish to study circumstances related to this RF response with particular reference to the role of therapy. The time relationship between commencing chemotherapy and conversion to RF seropositivity will be studied. Perhaps this auto-antibody response occurs following the release of antigenic matter from tumors with therapy. This will be studied by measurements of CEA in serial collections of serum from patients with colonic neoplasms. These specimens will also be tested for antigen-antibody complexes, in which form IgG is likelier to be immunogenic. We have not been able to demonstrate Ig, complement components or the binding of aggregated Ig on tumor tissues whose cells are susceptible to RF cytotoxicity in vitro. Perhaps plasma provides essential amboceptor. If so, is this amboceptor IgG, is patient plasma a unique source of amboceptor and what effect do antigen-antibody complexes have upon the reaction? This aspect will be studied. We have clearly shown that RF is toxic to tumor but not normal bladder mucosal cells, using a sensitive, simple protease digestion test. Additional cytotoxicity and immunofluorescence studies are planned on bladder, lung and colon carcinomas, malignant melanomas, glioblastomas, various sarcomas and on cells from normal tissues.